Mostrar el registro sencillo del ítem

dc.contributor.author
Lopez, Pablo
dc.contributor.author
Aja, Susan
dc.contributor.author
Aoki, Kazuhiro
dc.contributor.author
Seldin, Marcus M.
dc.contributor.author
Lei, Xia
dc.contributor.author
Ronnett, Gabriele V
dc.contributor.author
Wong, G. William
dc.contributor.author
Schnaar, Ronald L.
dc.date.available
2018-11-07T14:31:04Z
dc.date.issued
2017-01-05
dc.identifier.citation
Lopez, Pablo; Aja, Susan; Aoki, Kazuhiro; Seldin, Marcus M.; Lei, Xia; et al.; Mice lacking sialyltransferase ST3Gal-II develop late-onset obesity and insulin resistance; Oxford Univ Press Inc; Glycobiology; 27; 1; 5-1-2017; 129-139
dc.identifier.issn
0959-6658
dc.identifier.uri
http://hdl.handle.net/11336/63851
dc.description.abstract
Sialyltransferases are a family of 20 gene products in mice and humans that transfer sialic acid from its activated precursor, CMP-sialic acid, to the terminus of glycoprotein and glycolipid acceptors. ST3Gal-II (coded by the St3gal2 gene) transfers sialic acid preferentially to the three positions of galactose on the Galβ1-3GalNAc terminus of gangliosides GM1 and GD1b to synthesize GD1a and GT1b, respectively. Mice with a targeted disruption of St3gal2 unexpectedly displayed lateonset obesity and insulin resistance. At 3 months of age, St3gal2-null mice were the same weight as their wild type (WT) counterparts, but by 13 months on standard chow they were visibly obese, 22% heavier and with 37% greater fat/lean ratio than WT mice. St3gal2-null mice became hyperglycemic and displayed impaired glucose tolerance by 9 months of age. They had sharply reduced insulin responsiveness despite equivalent pancreatic islet morphology. Analyses of insulin receptor (IR) tyrosine kinase substrate IRS-1 and downstream target Akt revealed decreased insulininduced phosphorylation in adipose tissue but not liver or skeletal muscle of St3gal2-null mice. Thin-layer chromatography and mass spectrometry revealed altered ganglioside profiles in the adipose tissue of St3gal2-null mice compared to WT littermates. Metabolically, St3gal2-null mice display a reduced respiratory exchange ratio compared to WT mice, indicating a preference for lipid oxidation as an energy source. Despite their altered metabolism, St3gal2-null mice were hyperactive. We conclude that altered ganglioside expression in adipose tissue results in diminished IR sensitivity and late-onset obesity.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford Univ Press Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Adipose Tissue
dc.subject
Ganglioside
dc.subject
Hyperglycemia
dc.subject
Metabolism
dc.subject
Sialic Acid
dc.subject.classification
Inmunología
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Mice lacking sialyltransferase ST3Gal-II develop late-onset obesity and insulin resistance
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-10-22T15:50:34Z
dc.identifier.eissn
1460-2423
dc.journal.volume
27
dc.journal.number
1
dc.journal.pagination
129-139
dc.journal.pais
Reino Unido
dc.journal.ciudad
Oxford
dc.description.fil
Fil: Lopez, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Aja, Susan. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Aoki, Kazuhiro. University of Georgia; Grecia
dc.description.fil
Fil: Seldin, Marcus M.. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Lei, Xia. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Ronnett, Gabriele V. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Wong, G. William. Johns Hopkins University School of Medicine; Estados Unidos
dc.description.fil
Fil: Schnaar, Ronald L.. Johns Hopkins University School of Medicine; Estados Unidos
dc.journal.title
Glycobiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1093/glycob/cww098
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/glycob/article/27/2/129/2585095